Smoking More Lethal than HIV

Smoking kills. And among people with well-controlled HIV, that old slogan is even more true, researchers reported.

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Smokers with HIV had substantially higher rates of all-cause and non-AIDS mortality than HIV-positive non-smokers, with more than 60% of deaths among HIV patients associated with smoking.

Note that HIV-infected smokers lost more life-years to smoking than to HIV-related causes.

Smoking kills. And among people with well-controlled HIV, that old slogan is even more true, researchers reported.

In a large case-control study, smokers with HIV had substantially higher rates of all-cause and non-AIDS mortality than HIV-positive nonsmokers, according to Marie Helleberg, MD, of Copenhagen University Hospital, and colleagues.

Also, HIV-infected smokers lost more life-years to smoking than to HIV-related causes, Helleberg and colleagues reported online in Clinical Infectious Diseases.

The study, carried out in Denmark, establishes the risks of smoking in a situation where HIV care is integrated and anti-retroviral therapy is available at no cost.

The bottom line, Helleberg said in a statement, is that "more than 60% of deaths among HIV patients are associated with smoking," compared with slightly more than a quarter associated with HIV.

In the general population, Helleberg and colleagues noted, smoking is one of the major factors that reduce life expectancy.

Among those with HIV, the advent of highly active anti-retroviral therapy (HAART) has meant that lifestyle factors are increasingly affecting survival, while the mortality risk associated with the virus has diminished.

To pin down the effects of smoking on people whose HIV is well controlled, the researchers turned to the Danish HIV Cohort Study, a population-based nation-wide study that includes all HIV-infected individuals treated at Danish HIV centers after Jan. 1, 1995.

They analyzed outcomes for all members of the cohort who were older than 16 when they were diagnosed, were treated between Jan. 1, 1995 and Aug. 1 2010, and had smoking status at the time of diagnosis available. Injection drug users were excluded.

All told, the researchers reported, the HIV-positive study population included 2,921 people, who were matched for sex and year of birth with up to 4 controls each – a total of 10,642 individuals -- from the prospective Copenhagen General Population Study.

The two groups were followed for 14,281 and 45,122 person-years, respectively, yielding a median follow-up time of 4.2 years for patients and 4.1 years for controls.

As expected, the HIV-positive participants smoked more heavily than the controls -- 47.4% were current smokers, 17.7% had previously smoked, and 34.9% were never smokers compared with 20.6%, 32.8%, and 46.6%, respectively among the controls.

Over the study period, there were 221 deaths in this HIV-positive cohort, including 58 (26%) related to the virus. There were also 142 deaths from non-AIDS related causes (64%). The remaining 21 deaths (10%) were attributed to violence.

Among the controls, there were 132 deaths from all causes.

When the researchers broke down the deaths by smoking status they found that all-cause mortality was substantially higher among smoking HIV patients compared with nonsmokers. The mortality rate ratio (MRR) was 4.4 (95% CI 3.0 to 6.7).

MRR for non-AIDS mortality was even higher at 5.3 (95% CI 3.2 to 8.8).

In contrast, among controls, the MRR was 3.5 (95% CI 2.2 to 5.5), when comparing current and never smokers.

The excess mortality rate per 1,000 person-years among current smokers versus non-smokers was 17.6 for HIV patients and 4.8 for controls.

A 35-year-old HIV-positive smoker had a median life expectancy of 62.6 years, compared with 69.1 years for previous smokers and 78.4 years for never-smokers.

Among never-smokers, having HIV led to 5.1 years of life lost, compared with the controls, Helleberg and colleagues found. That was greater than the 3.6 years lost when smoking controls were compared with nonsmokers.

But the greatest disparity was the 12.3 years of life expectancy lost when HIV-positive smokers were compared with HIV-positive never-smokers, they reported.

Helleberg and colleagues cautioned that it is possible that mortality among the controls was underestimated, which would tend to inflate mortality among the HIV-positive cohort.

Although the analysis accounted for a range of possible confounding factors, they added, residual confounding, and socioeconomic status in particular is likely.

The study had support from the University of Copenhagen. The journal said Helleberg reported no conflicts.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco

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